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November 24, 2008

Experimental Antiviral Drug Shows Promise

by Sam Savage

U.S. researchers said on Sunday that an experimental drug cured guinea pigs infected with a fatal hemorrhagic fever virus, raising hope for its use in a broad range of viral diseases including influenza, hepatitis C, HIV, Ebola and others.

Dr. Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center at Dallas, said the study sparks a whole new strategy for making antiviral drugs.

Thorpe said rather than attacking the virus directly, bavituximab, made by Peregrine Pharmaceuticals, takes advantage of a defense mechanism used by the virus to hide from the immune system.

When cells are under attack by a virus, this stress causes a fat molecule called phosphatidylserine, which normally lines the inside of the cell, to flip to the outside.

Bavituximab is a genetically engineered antibody that seeks out and attaches itself to these turncoat cells, flagging them for the immune system, which can then mount an attack.

Thorpe said that when injected into the bloodstream, bavituximab circulates in the body until it finds these inside-out lipids and then binds to them.

"In the case of virus infection, the binding raises a red flag to the body's immune system, forcing the deployment of defensive white blood cells to attack the infected cells."

"Conventional antiviral drugs try to exploit some property of the virus, but these drugs are often quickly defeated as the virus mutates," he added.

He said that by targeting an aspect of infected cells in the host, bavituximab is less likely to lose effectiveness, which is common when a virus mutates.

Thorpe and his colleagues tested the compound on guinea pigs in an advanced stage of infection with a form of the Lassa fever virus, a disease that affects parts of West Africa.

During the study, half of the animals treated with the drug alone were cured. When the researchers tested it in combination with the antiviral drug ribavirin, a drug that keeps a virus from replicating, 63 percent of the guinea pigs lived.

According to Thorpe, the drug might be effective on other types of hemorrhagic viruses, such as Ebola and Marburg. But this lipid flipping also occurs in cells infected with many other viral infections, including influenza, smallpox and rabies.

Early phase clinical trials of the drug are being tested in people with hepatitis C and human immunodeficiency virus, or HIV, which causes AIDS. Additionally, Peregrine said it has more advanced trials under way in cancer.

Steven King, president and chief executive of Peregrine, said he thinks it has tremendous potential.

Peregrine and the National Institutes of Health funded the study.

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Image 2: Drs. Philip Thorpe, professor of pharmacology, and Melina Soares, instructor of pharmacology, have shown that an anti-viral drug developed at UT Southwestern shows promise as a new strategy to fight viral diseases. Credit: UT Southwestern Medical Center